Folinic acid is used in cancer chemotherapy, to counteract the side-effects of treatments involving the drug methotrexate, or in synergistic combination with the chemotherapy agent 5-fluorouracil. Folinic acid is generally administered in the form of its calcium or sodium salts.
Folinic acid exists in diastereoisomeric forms, depending on the R or S configuration at the carbon atoms identified as chiral in the structural formula below:

The chiral carbon atom in the glutamic acid moiety retains the structure of the natural aminoacid. The other chiral center is the carbon atom identified as 6 in the formula above; as it happens with most biological enantiomeric molecules, only the form with configuration S at this carbon, that is, the compound (6S)—N(5)-formyl-5,6,7,8-tetrahydrofolic acid, is biologically active. This form of the acid is commonly referred to in the field as levofolinic acid, and its salts as levofolinates, terms that will be adopted in the description that follows and in the claims.
Diastereomerically enriched or pure forms of levofolinic acid are generally produced, directly in form of pharmaceutically acceptable salts, through crystallization.
An example of such processes is given in U.S. Pat. No. 5,134,235, disclosing the production of alkaline-earth salts of levofolinic acid in enriched form compared to the racemic mixture.
Patent application US 2008/0153849 A1 discloses a method by which it is possible to prepare either the racemic mixture of dextrofolinic and levofolinic acid in crystalline form, or pure levofolinic acid in amorphous form.
At present, it is not known yet a method affording the preparation of essentially pure levofolinic acid in crystalline form; the production of this compound, in a diastereoisomerically pure form, is desirable, as it would provide a convenient way of producing pharmaceutical salts of the acid in 6S pure form and could also be directly used for new pharmaceutical formulation without needing the previous preparation of a salt.
It is thus object of the present invention to provide the compound (6S)—N(5)-formyl-5,6,7,8-tetrahydrofolic acid in diastereoisomerically pure and stable crystalline form, as well as a process for its preparation.